“Cosmetic surgery” is a phrase used to describe broadly surgical changes made to a human body with the usual, though not always, justification of enhancing appearance. This area of medical practice constitutes an ever-growing industry around the world. Obviously, where such a procedure fails to deliver an enhanced appearance, the procedure fails to meet the desired goal. One of the reasons that the majority of current procedures fail to deliver upon their promise is that, for the most part, current procedures are invasive, requiring incisions and suturing, and can have serious and unpleasant side effects, including but not limited to scarring, infection, and loss of sensation.
One of the more common forms of cosmetic surgery is the “face-lift.” A face-lift is intended to enhance facial appearance by removing excess facial skin and tightening the remaining skin, thus removing wrinkles. A face-lift is traditionally performed by cutting and removing portions of the skin and underlying tissues on the face and neck. Two incisions are made around the ears and the skin on the face and neck is separated from the subcutaneous tissues. The skin is stretched, excess tissue and skin are removed by cutting with a scissors or scalpel, and the skin is pulled back and sutured around the ears. The tissue tightening occurs after healing of the incisions because less skin covers the same area of the face and neck and also because of the scars formed on the injured areas are contracting during the healing process.
Traditional face-lift procedures are not without potential drawbacks and side effects. One drawback of traditional cosmetic surgery is related to the use of scalpels and scissors. The use of these devices sometimes leads to significant bleeding, nerve damage, possible infection and/or lack of blood supply to some areas on the skin after operation. Discoloration of the skin and alopecia (baldness) are other possible side effects of the standard cosmetic surgery. The overall quality of the results of the surgery is also sometimes disappointing to the patients because of possible over-corrections, leading to undesired changes in the facial expression. Additionally, face-lift procedures require a long recovery period before swelling and bruising subside.
The use of lasers to improve the appearance of the skin has been also developed. Traditional laser resurfacing involves application of laser radiation to the external layer of the skin—the epidermis. Destruction of the epidermis leads to rejuvenation of the epidermis layer. The drawback of the laser resurfacing procedure is possible discoloration of the skin (red face) that can be permanent.
Another laser procedure involves using optical fibers for irradiation of the subcutaneous tissues, such as disclosed in U.S. Pat. No. Re36,903. This procedure is invasive and requires multiple surgical incisions for introduction of the optical fibers under the skin. The fibers deliver pulsed optical radiation that destroys the subcutaneous tissues as the tip of the fiber moves along predetermined lines on the face or neck. Debulking the subcutaneous fat and limited injury to the dermis along the multiple lines of the laser treatment results in contraction of the skin during the healing process, ultimately providing the face lift. The drawback of the method is its high price and possibility of infection.
Electrosurgical devices and methods utilizing high frequency electrical energy to treat a patient's skin, including resurfacing procedures and removal of pigmentation, scars, tattoos and hairs have been developed lately, such as disclosed in U.S. Pat. No. 6,264,652. The principle drawback of this technology is collateral damage to the surrounding and underlying tissues, which can lead to forming scars and skin discoloration.
Other forms of cosmetic surgery are also known. One example is liposuction, which is an invasive procedure that involves inserting a suction device under the skin and removing fat tissues. As with other invasive surgical procedures, there is always a risk of infection. In addition, because of the invasive nature of the procedure, physicians usually try to minimize the number of times the procedure must be performed and thus will remove as much fat tissue as possible during each procedure. Unfortunately, this procedure has resulted in patient deaths when too much tissue was removed. Assuming successful removal of excess fat tissue, further invasive surgery may be required to accomplish desired skin tightening.
The prior art to date, then, does not meet the desired goal of performing cosmetic surgery in a non-invasive manner while causing minimal or no scarring of the exterior surface of the skin and at the same time resulting in the skin tightening.
The term “electroporation” (EP) is used herein to refer to the use of a pulsed electric field to induce microscopic pores in the biological membranes, also commonly called a cell wall, of living cells. The cell membrane separates the inner volume of a cell, or cytosol, from the extracellular space, which is filled with lymph. This membrane performs several important functions, not the least of which is maintaining gradients of concentration of essential metabolic agents across the membrane. This task is performed by active protein transporters, built in the membrane and providing transport of the metabolites via controlled openings in the membrane. Normally, the active protein transporters, or pumps, which routinely provide transport of various metabolic agents, especially proteins, across the cell membrane, use either the energy of positive ions (hydrogen or sodium ions) passing from the positive potential of the intracellular space to the negative potential of the cytosol, or the energy of negative ions (chlorine ions) for movement across the membrane in the opposite direction. This energy supply for the protein transporters is provided by maintaining the potential difference across the membrane, which, in turn, is linked to the difference in concentrations of sodium and potassium ions across the membrane. When this potential difference is too low, thousands of the active transporters find themselves out of power.
Inducing relatively large pores in the cell membrane by electroporation creates the opportunity for a fluid communication through the pores between the cytosol and the extracellular space that may lead to a drastic reduction of these vitally important gradients of concentrations of the metabolic agents and thus a reduction in the potential difference across the membrane. Uncontrolled exchange of metabolic agents, such as ions of sodium, potassium, and calcium between a living cell and the extracellular space imposes on the cell intensive biochemical stress.
When a cell is undergoing biochemical stresses the major biochemical parameters of the cell are out of equilibrium and the cell cannot perform its routine functions. Invasion of very high concentration of calcium ions through membrane pores from the interstitial space between cells, where the calcium ion concentration is about 100 times higher than in the cytosol, can create such stresses by reducing the potential difference across the membrane. In an attempt to repair itself, the cell starts working in a damage control mode: an emergency production of actin filaments is triggered that extend across the large pores in the membrane in an attempt to bridge the edges of the pores, pull the edges together, and thereby seal the membrane. In muscle cells the calcium ion invasion may cause lethal structural damage by forcing the cell to over-contract and rupture itself. Small pores in the membrane created by a relatively short electric pulse can reseal themselves spontaneously and almost instantaneously after the removal of electric field. No significant damage to the cell is done in this case. Contrary to that, larger pores may become meta-stable with very long life time and cause irreversible damage. It can be said that, depending on the number, effective diameter -and life time of pores in the membrane, electroporation of the cell may result in significant metabolic or structural injury of the cell and/or its death. The cause of cell death after electroporation is believed to be an irreversible chemical imbalance and structural damage resulted from the fluid communication of the cytosol and the extracellular environment.
Below a certain limit of the electric field no pores are induced at all. This limit, usually referred to as the “lower EP limit” of electroporation, is different for different cells, depending, in part, on their sizes in an inverse relationship. That is, pores are induced in larger cells with smaller electric fields while smaller cells require larger electric fields. Above the lower EP limit the number of pores and their effective diameter increase with both the amplitude and duration of the electric field pulses.
Removing the electric field pulses enables the induced pores to reseal. This process of resealing of the pores and the ability of the cell to repair itself, discussed briefly above, currently is not well understood. The current understanding is that there is a significant range of electric field amplitudes and pulse durations in which cells survive electroporation and restore their viability thereafter. An electroporated cell may have open pores for as long as many minutes and still survive. The range of electric field amplitudes and pulse durations in which cells survive is successfully used in current biomedical practice for gene transfer and drug delivery inside living cells.
Nevertheless, the survivability of electroporated cells is limited As the electric field amplitude and/or duration of pulses, increases, this limit, usually referred to as the “upper EP limit” of electroporation, is inevitably achieved. Above the upper EP limit, the number and sizes of pores in the cellular membrane become too large for a cell to survive. Multiple pulses cause approximately the same effect on the cells as one pulse with a duration equal to the total duration of all applied pulses. After application of an electrical pulse above the upper electroporation limit the cell cannot repair itself by any spontaneous or biological process and dies. The upper EP limit is defined by the combinations of the amplitudes of electric field and pulse durations that cause cellular death.
The vulnerability of cells to electroporation depends on their size: the larger the cell, the lower the electric field and duration of a pulse capable of killing it. If cells of different sizes are exposed to the same electric field, the largest cells will die first. Thus, this ability of electroporation to discriminate cells by their sizes may be used to selectively kill large cells in the human body.
In the previously referred to application for U.S. patent application entitled “Apparatus and Method for Reducing Subcutaneous Fat Deposits, Virtual Face Lift and Body Sculpting by Electroporation”, Ser. No. 09/931,672, filed Aug. 17, 2001, an apparatus and method for performing non-invasive treatment of the human face and body by electroporation in lieu of cosmetic surgery is disclosed. The apparatus comprises a high voltage pulse generator and an applicator having two or more electrodes utilized in close mechanical and electrical proximity with the patient's skin to apply electrical pulses thereto. The applicator may include at least two electrodes with one electrode having a sharp tip and another having a flat surface. High voltage pulses delivered to the electrodes create at the tip of the sharp electrode an electric field high enough to cause death of relatively large subcutaneous fat cells by electroporation. Moving the electrode tip along the skin creates a line of dead subcutaneous fat cells, which later are metabolized by the body. Multiple applications of the electrode along predetermined lines on the face or neck create shrinkage of the skin and the subcutaneous fat reduction under the treated area.
The electroporation in-vivo, employed in the disclosed method is a non-invasive treatment of subcutaneous fat, which, as was previously described before, involves application of high amplitude electric pulses between external electrodes to cause death by electroporation of the subcutaneous fat cells. Fat cells, being typically larger than other cells of the body, are more easily killed by electroporation treatment than are smaller lean muscle cells. The electric field, applied to the external electrodes, is efficient for cell killing in the subcutaneous layer of fat tissue directly under the skin. However, the amplitude of the field significantly decreases with increasing the depth of the deposits of fat cells. The deeper penetration of the electric field may be achieved by increasing the distance between electrodes with simultaneous increase in the operating voltage. This approach, though, leads to concomitant increase of the volume that is treated by electroporation. Occasionally, during such cosmetic and body sculpting procedures as described above, a small volume of deep subcutaneous fat deposit must be treated. The non-invasive method of treating subcutaneous tissue by electroporation as described in the earlier referenced patent application, in which the high voltage pulses are applied to the external electrodes, is sometimes difficult to apply to deep fat deposits especially when a fine spatial resolution is required
It would be desirable to have available an apparatus and a method for electroporation treatment to reduce deep fat deposits by allowing deep localized application of the electroporation pulses that can provide high spatial resolution of the body sculpting. Preferably, such apparatus and methods would also be minimally invasive.